P1045: DISEASE PROGRESSION AND LEUKEMIC TRANSFORMATION IN PATIENTS WITH LOWER-RISK MYELOFIBROSIS: AN ANALYSIS FROM MOST
Authors: Rami S. Komrokji, Michael Grunwald, Evan Braunstein, J.E. Hamer-Maansson, Tricia Kalafut, John Mascarenhas
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: Progressive disease (PD) in myelofibrosis (MF) is associated with increased bone marrow fibrosis, worsening anemia, and increased circulating blasts, and can result in leukemic transformation (LT), a rare but fatal complication. Real-world data regarding PD and LT in patients (pts) with lower-risk MF are limited. Aims: This analysis from the Myelofibrosis and Essential Thrombocythemia Observational Study (MOST; NCT02953704) describes the incidence of PD, including LT, in pts with lower-risk MF and compares baseline characteristics of pts who developed PD with those who did not. Methods: MOST is a longitudinal, noninterventional, prospective study of pts with MF or essential thrombocythemia enrolled at US clinical practices. Pts (≥18 y) with low-risk or intermediate-1– (INT-1) risk MF (by age >65 y alone) stratified by the Dynamic International Prognostic Scoring System (Blood. 2010;115:1703) were eligible, and were followed for ≥3 y. Baseline data were collected as previously described (Gerds. CLML. 2022). PD was defined as physician-reported PD for any reason, and/or LT, and/or death due to PD during the study. Results: Of 232 pts with MF enrolled in MOST, 204 were analyzed (with PD, n=59; without PD, n=134; unknown, n=11; cutoff: Sept 30, 2022). Median time from MF diagnosis to enrollment was 1.8 (range, 0-38) y; median enrollment duration was 4.4 (range, 3.5-5.6) y. Pts with PD were older vs pts without PD, and a larger percentage of Black vs White pts had PD (Table). A smaller percentage of pts who had PD vs without PD were employed (20.3% vs 44.4%, P=0.0003) and a larger percentage were unable to work (16.9% vs 2.3%). Among the 59 pts (28.9%) with PD, percentages of pts with physician-reported indicators of PD in descending order of frequency were change in hematologic parameters (45.8%), change in spleen size (32.2%), change in MF symptoms (27.1%), and change in blast counts (13.6%), LT occurrence (25.4%), and death due to PD (20.3%). For low- vs INT-1–risk groups, percentages of pts with change in blast counts was higher (20.0% vs 10.3%), LT occurrence was lower (20.0% vs 28.2%), and death due to PD was lower (10.0% vs 25.6%). Differences in symptomology of pts with PD vs without PD at enrollment were not statistically significant (Table). Summary/Conclusion: This real-world analysis of MOST describes disease evolution in pts with lower-risk MF. About one-third of pts had PD; compared with pts without PD, pts with PD were older, less likely to be employed or able to work, and more likely to be Black. The finding that a higher percentage of pts with PD were receiving RUX vs HU at enrollment, and pts receiving RUX were more likely to have signs of progression (older age, splenomegaly, longer disease duration), suggests that RUX use was greater in pts at higher risk for PD. Further longitudinal analyses from MOST will provide additional insight into risk factors for PD to facilitate improved disease management and outcomes for pts with lower-risk MF.Keywords: Myelofibrosis, Leukemic transformation, Progression